Immunotherapy (allergen injection therapy) is in common use in the treatment of childhood allergic asthma. Most of the existing clinical studies purporting to demonstrate the efficacy of this form of treatment are experimentally flawed, or do not address the clinically relevant issue of multiple allergen immunotherapy for perennial asthmatic symptoms. The principal objective of this research has been to mount a prospective, randomized, double-blind clinical trial to evaluate the effectiveness of optimal allergen immunotherapy on the severity and course of perennial asthma in atopic children. A group of allergic asthmatic children, age 5 - 12, are being characterized according to disease severity and medication requirements. Following a period of medication stabilization and baseline observations, each is randomized to receive placebo or active immunotherapy with aqueous extracts of pertinent environmental allergens. Treatment is given biweekly for 30 months, followed by an open follow-up period of 2 - 4 years. One team of investigators will remain blinded to supervise clinical care; a second unblinded team will administer the immunotherapy. Disease severity is being assessed primarily by the type and quantity of medication required to achieve acceptable symptom scores and pulmonary function tests. Medications are adjusted frequently to maintain symptoms and pulmonary function within targeted limits. The study was initiated in 1985 and substantial progress has been made with 53 subjects randomized as of April 1988. Recruitment will continue until at least 100 evaluable subjects have completed the randomized study. Additional research objectives will be pursued in this same set of well- characterized asthmatic children. First, the natural history of airway hyperreactivity to non-specific stimuli will be evaluated using periodic methacholine inhalation tests. The effect of immunotherapy on airway hyperreactivity will be determined by comparing changes in active treatment and placebo groups. Second, the benefit of environmental analysis of the home will be studied. Clinically significant household allergens including animal dander, dust mites (Dermatophagoides species), and common mold spores will be assessed by home inspections and antigenic analysis of aqueous extracts of housedust samples. Third, the clinical trial database will be used to examine pertinent clinical questions including the predictive value of home peak flow measurements and symptom diaries for exacerbations of asthma, and the correlation of allergic sensitivities to seasonal exacerbations. Finally, the effect of high-dose, long-term immunotherapy on parameters of target cell sensitivity in children will be examined.